Porphyromonas gingivalis is an invasive anaerobe implicated in periodontal tissue destruction and cardiovascular disease. P. gingivalis invades highly vascularized gingival tissues, gaining access to iron and other nutritional sources. We have observed that the invasive ability of various P. gingivalis strains varies by as much as three orders of magnitude. This is most likely explained by genetic polymorphisms present on the P. gingivalis genome. It is thus our hypothesis that this invasion variability reflects inter-strain genomic heterogeneity. Consequently, our goal is to use microarray comparative genomic hybridization (CGH) analysis of P. gingivalis strains that have diverse invasion abilities in order to identify the invasion-associated subset of bacterial genes within the invasive genotype. Identification of unique invasion-associated virulence factors will lead to a better understanding of the putative virulence mechanisms and genetic heterogeneity of this organism. This approach will also likely identify moieties involved in cross talk between the invasive bacteria and the host tissue. Such information should facilitate the development of novel defined molecular approaches for the treatment of periodontitis. 7. Public Health Significance: Porphyromonas gingivalis is a bacterium found in gum disease and in plaques from heart disease. The goal of this project is to learn more about how P. gingivalis enters human cells to cause disease. This knowledge may allow us to develop new, more effective treatments for diseases of the gums and heart.